Several vasodilator mechanisms may play a role in local metabolic control of coronary vascular resistance. Previous studies have implicated adenosine, K ion, vessel wall pO2 and pCO2, and prostaglandins. Some of these mechanisms may be important only in certain circumstances (e.g. when the myocardium is hypoxic) and others only in transient as opposed to steady state situations. We propose to observe the changes in coronary sinus pO2, pCO2, K ion, and prostaglandins and myocardial adenosine during alterations in the metabolic activity of the heart caused by cardiac pacing, isoproterenol infusion, and carotid sinus hypotension. We then plan to interfere with each of the proposed vasodilator mechanisms using maneuvers such as changes in arterial pCO2 and pO2, and administration of thyroid hormone, ouabain, aminophylline, and indomethacin and observe the changes in coronary vascular resistance and the vasodilator substances associated with the same increase in metabolic activity. In addition we will study the effect on the various metabolic vasodilator systems of holding coronary blood flow at a low level during increased metabolic activity. We have found that the tissue hypoxia associated with a period of increased metabolic activity in the circumstance is followed by a prolonged vasodilation. We will be especially interested in determining which of the vasodilator mechanisms are responsible for this vasodilation. Because we will measure changes in each of the five vasodilator mechanisms in the same preparations and because we will observe transient as well as steady state changes, these experiments should allow us to determine the relative contributions of the various vasodilator systems to the local metabolic control of coronary blood flow in a variety of circumstances.